Identifying susceptibility of a subject to cardiac therapy based on determination of a cardiac troponin, scd40l, and c-reactive protein

Abstract

Disclosed is a method for identifying a subject being susceptible to a cardiac therapy based on determination of a cardiac troponin T and the additional determination of C-reactive protein (CRP) or sCD40L (soluble CD40 ligand) in a sample of a subject with stable coronary heart disease and a history of an acute cardiovascular event. Also disclosed is a method for predicting the risk of mortality and/or a further acute cardiovascular event for a subject with stable coronary heart disease and a history of acute cardiovascular event based on the determination of the aforementioned markers. Further disclosed are kits and devices adapted to carry out the disclosed methods.

What is claimed is: 
     
         1 . A method for identifying susceptibility of a subject to a cardiac therapy, wherein the subject suffers from stable coronary heart disease and has a history of at least one acute cardiovascular event, the method comprising the steps of:
 determining an amount of a cardiac troponin in a sample from the subject,   comparing the amount of the cardiac troponin determined to a reference amount of the cardiac troponin, and   if the determined amount of the cardiac troponin is larger than the reference amount of the cardiac troponin, then also determining an amount of C-reactive protein (CRP) in a sample from the subject and comparing the determined amount of CRP to a reference amount of CRP, or if the determined amount of the cardiac troponin is lower than the reference amount of the cardiac troponin, then also determining an amount of soluble CD40L ligand (sCD40L) in a sample from the subject and comparing the determined amount of sCD40L to a reference amount of sCD40L, wherein   an amount of the cardiac troponin larger than the reference amount of the cardiac troponin and an amount of the C-reactive protein larger than the reference amount of the C-reactive protein is indicative for high susceptibility of the subject to the cardiac therapy,   an amount of the cardiac troponin larger than the reference amount of the cardiac troponin and an amount of the C-reactive protein lower than the reference amount of the C-reactive protein is indicative for susceptibility of the subject to the cardiac therapy,   an amount of the cardiac troponin lower than the reference amount of the cardiac troponin and an amount of sCD40L larger than the reference amount of sCD40L is indicative for susceptibility of the subject to the cardiac therapy, and   an amount of the cardiac troponin lower than the reference amount of the cardiac troponin and an amount of sCD40L lower than the reference amount of sCD40L is indicative for non-susceptibility of the subject to the cardiac therapy.   
     
     
         2 . The method of  claim 1 , wherein the cardiac troponin is troponin T. 
     
     
         3 . The method of  claim 1 , wherein the cardiac therapy is a drug-based therapy or an interventional therapy. 
     
     
         4 . The method of  claim 1 , wherein the at least one acute cardiovascular event occurred more than six months ago. 
     
     
         5 . The method of  claim 1 , wherein the sample is a blood, blood plasma, or a blood serum sample. 
     
     
         6 . The method of  claim 1 , wherein the reference amount of the cardiac troponin is 0.007 ng/ml and the cardiac troponin is troponin T, the reference amount of C-reactive protein is 2.8 μg/ml, and the reference amount of sCD40L is 2.0 μg/ml. 
     
     
         7 . A method for predicting a risk of mortality or a further acute cardiovascular event in a subject, wherein the subject suffers from stable coronary heart disease and has a history of at least one acute cardiovascular event, the method comprising the steps of:
 determining an amount of a cardiac troponin in a sample from the subject,   comparing the amount of the cardiac troponin determined to a reference amount of the cardiac troponin, and   if the determined amount of the cardiac troponin is larger than the reference amount of the cardiac troponin, then also determining an amount of C-reactive protein (CRP) in a sample from the subject and comparing the determined amount of CRP to a reference amount of CRP, or if the determined amount of the cardiac troponin is lower than the reference amount of the cardiac troponin, then also determining an amount of soluble CD40L ligand (sCD40L) in a sample from the subject and comparing the determined amount of sCD40L to a reference amount of sCD40L, wherein   an amount of the cardiac troponin larger than the reference amount of the cardiac troponin and an amount of the C-reactive protein larger than the reference amount of the C-reactive protein is indicative for a significantly elevated risk of mortality or further acute cardiovascular event in the subject,   an amount of the cardiac troponin larger than the reference amount of the cardiac troponin and an amount of the C-reactive protein lower than the reference amount of the C-reactive protein is indicative for an elevated risk of mortality or further acute cardiovascular event in the subject,   an amount of the cardiac troponin lower than the reference amount of the cardiac troponin and an amount of sCD40L larger than the reference amount of sCD40L is indicative for an elevated risk of mortality or further acute cardiovascular event in the subject, and   an amount of the cardiac troponin lower than the reference amount of the cardiac troponin and an amount of sCD40L lower than the reference amount of sCD40L is indicative for no increased risk of mortality or further acute cardiovascular event in the subject.   
     
     
         8 . The method of  claim 7 , wherein the reference amount of the cardiac troponin is 0.007 ng/ml and the cardiac troponin is troponin T, the reference amount of C-reactive protein is 2.8 μg/ml, and the reference amount of sCD40L is 2.0 pμg/ml. 
     
     
         9 . A method for identifying susceptibility of a subject to a cardiac therapy, wherein the subject has stable coronary heart disease, a history of at least one acute cardiovascular event, and a cardiac troponin level of lower than 0.007 ng/ml, the method comprising the steps of:
 determining an amount of C-reactive protein (CRP) in a sample from a subject,   comparing the amount of CRP determined to a reference amount of CRP, and   identifying susceptibility of the subject to the cardiac therapy if the amount of CRP determined is larger than the reference amount of CRP.   
     
     
         10 . A method for identifying susceptibility of a subject to a cardiac therapy, wherein the subject has stable coronary heart disease, a history of at least one acute cardiovascular event, and a cardiac troponin level of lower than 0.007 ng/ml, the method comprising the steps of:
 determining an amount of soluble CD40L ligand (sCD40L) in a sample from a subject,   comparing the amount of sCD40L determined to a reference amount of sCD40L, and   identifying susceptibility of the subject to the cardiac therapy if the amount of sCD40L determined is larger than the reference amount of sCD40L.   
     
     
         11 . A device for identifying susceptibility of a subject to a cardiac therapy according to the method of  claim 1 , the device comprising:
 means for determining an amount of a cardiac troponin in a sample from the subject, and means for comparing the amount determined with a reference amount of the cardiac troponin,   means for determining an amount of CRP in a sample from the subject and means for comparing the amount determined to a reference amount of CRP, and   means for determining an amount of sCD40L in a sample from the subject and means for comparing the amount determined to a reference amount of sCD40L,   whereby susceptibility of a subject to a cardiac therapy is identified.   
     
     
         12 . A device for predicting a risk of mortality or a further acute cardiovascular event in a subject according to the method of  claim 7 , the device comprising:
 means for determining an amount of a cardiac troponin in a sample from the subject, and means for comparing the amount determined with a reference amount of the cardiac troponin,   means for determining an amount of CRP in a sample from the subject and means for comparing the amount determined to a reference amount of CRP, and   means for determining an amount of sCD40L in a sample from the subject and means for comparing the amount determined to a reference amount of sCD40L,   whereby a prediction of a risk of mortality or further acute cardiovascular event is made.   
     
     
         13 . A kit adapted for identifying susceptibility of a subject to a cardiac therapy according to the method of  claim 1 , the kit comprising:
 instructions for carrying out the method,   means for determining an amount of a cardiac troponin in a sample from the subject,   means for determining an amount of CRP in a sample from the subject, and   means for determining an amount of sCD40L in a sample from the subject.   
     
     
         14 . A kit adapted for predicting a risk of mortality or a further acute cardiovascular event in a subject according to the method of  claim 7 , the kit comprising:
 instructions for carrying out the method,   means for determining an amount of a cardiac troponin in a sample from the subject,   means for determining an amount of CRP in a sample from the subject, and   means for determining an amount of sCD40L in a sample from the subject.